Blood Protein Can Reprogram Immune Cells to Inhibit Tumor Growth

A protein that occurs naturally in the blood has the ability to reprogram immune cells to prevent the growth and spread of tumors.

In cancerous tissue, tumor-associated M2 macrophages (TAMs) promote tumor growth while a minority of M1 macrophages acts against this. Under certain circumstances, M2 macrophages can be converted to the M1 class. Drugs to push macrophages in this direction are currently under development.

In the current study investigators at Uppsala University (Sweden) examined possible interactions between TAMs and the naturally occurring histidine-rich glycoprotein (HRG), which had previously been shown to inhibit tumor growth and metastasis, while improving chemotherapy.

The investigators worked with three different types of tumors growing in a mouse model. They reported in the January 6, 2011, online edition of the journal Cancer Cell that when HRG was present tumors grew more slowly and did not metastasize. The inhibiting effect was due to HRG down regulation of the protein placenta growth factor (PlGF). PlGF deficiency induced M2 macrophages to transform into M1 macrophages.

"Our study shows that the regulation of tumor-associated inflammation can be utilized to treat cancer and that there is a great potential to develop HRG into a drug for cancer treatment,” said contributing author Dr. Lena Claesson-Welsh, professor of immunology, genetics, and pathology at Uppsala University. "We are also looking into how HRG levels in the blood change in cancer, and the next step will be to find the binding sites for HRG on macrophages, so they can be used in developing drugs.”

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